Azoospermia, defined as the absence of sperm in the ejaculate, is a well-documented consequence of exogenous testosterone (ET) and anabolic-androgenic steroid (AAS) use. These agents suppress the hypothalamic-pituitary-gonadal (HPG) axis, leading to reduced intratesticular testosterone levels and impaired spermatogenesis. This review examines the pathophysiological mechanisms underlying azoospermia and outlines therapeutic strategies for recovery. Azoospermia is categorized into pretesticular, testicular, and post-testicular types, with a focus on personalized treatment approaches based on the degree of HPG axis suppression and baseline testicular function. Key strategies include discontinuing ET and monitoring for spontaneous recovery, particularly in patients with shorter durations of ET use. For cases of persistent azoospermia, gonadotropins (human chorionic gonadotropin [hCG] and follicle-stimulating hormone [FSH]) and selective estrogen receptor modulators (SERMs), such as clomiphene citrate, are recommended, either alone or in combination. The global increase in exogenous testosterone use, including testosterone replacement therapy and AAS, underscores the need for improved management of associated azoospermia, which can be temporary or permanent depending on individual factors and the type of testosterone used. Additionally, the manuscript discusses preventive strategies, such as transitioning to short-acting testosterone formulations or incorporating low-dose hCG to preserve fertility during ET therapy. While guidelines for managing testosterone-related azoospermia remain limited, emerging research indicates the potential efficacy of hormonal stimulation therapies. However, there is a notable lack of well-structured, controlled, and long-term studies addressing the management of azoospermia related to exogenous testosterone use, highlighting the need for such studies to inform evidence-based recommendations.
Humans ; Azoospermia/therapy* ; Male ; Testosterone/therapeutic use* ; Anabolic Agents/adverse effects* ; Clomiphene/therapeutic use* ; Chorionic Gonadotropin/therapeutic use* ; Follicle Stimulating Hormone/therapeutic use* ; Spermatogenesis/drug effects* ; Androgens/adverse effects*

Testosterone affects several organs in the body and is very important for male well-being. Aging men with late-onset hypogonadism (LOH) experience physiologic, psychiatric, and sexual symptoms related to a decline in the serum concentration of testosterone with age. However, it is well-known that the extent of the decline in testosterone concentration does not correlate with the severity of LOH-related symptoms. Therefore, it is difficult to diagnose and treat patients with LOH. In addition, the symptoms, response to testosterone replacement therapy (TRT), and medical insurance coverage differ among ethnicities and countries. The evaluation of testosterone is essential for the diagnosis and treatment of LOH. The effects of testosterone are determined not only by the serum testosterone concentration but also by the androgen receptor sensitivity. A low number of glutamine repeats is indicative of high androgenic activity, and the number shows ethnicity-related differences (fewer in African American than in Caucasian people and more in East Asian people). The diagnosis of LOH is typically made using subjective symptoms and the serum testosterone concentration. The Aging Male Symptoms scale is widely used to evaluate the symptoms. The normal range of total testosterone concentration varies around the world; therefore, clinicians should follow the guidelines of their regional academic society. The principal treatment for LOH is TRT. There are many types of TRT and other treatment strategies are also available. Thus, physicians should treat LOH according to each patient's situation, considering related disorders, such as diabetes, osteoporosis, metabolic syndrome, and depression.
Humans ; Male ; Hypogonadism/drug therapy* ; Testosterone/blood* ; Hormone Replacement Therapy/methods* ; Japan ; Age of Onset ; Aging ; Aged ; Androgens/therapeutic use*

INTRODUCTION: Rehabilitation medicine in a tertiary care hospital involves attending to many patients affected by intensive care unit (ICU)-associated weakness (ICU-AW) and hospital-associated deconditioning (HAD). These conditions contribute to poor long-term functional outcomes and increased mortality. We explored the role of short-term adjunctive androgen therapy in this group of patients in improving the rehabilitative outcomes. METHODS: This was a retrospective analysis of five patients with either ICU-AW or HAD who were given testosterone replacement therapy (TRT) or oxandrolone for a total of 2 weeks during the period from April to November 2020 was undertaken. During the 2-week trial period, the subjects underwent standard rehabilitation therapy. RESULTS: Grip strength was used as the primary outcome measure, and the mean improvement was 4.2 kg (+24.9%), which is encouraging in a 2-week timeframe. This was matched with good functional recovery in terms of distance ambulated and less assistance needed for ambulation. Sex hormone analysis was also done before initiation of TRT, and it showed that four out of five of the subjects were biochemically hypogonadal. None of the subjects dropped out or experienced any significant adverse events over the 2-week trial period. All the subjects except one improved to full independence at 3 months post-discharge. CONCLUSION TRT has the potential to be used as a useful adjunct to standard rehabilitation in enhancing functional recovery in critically ill patients. A multidisciplinary approach would ensure that suitable patients benefit from optimal nutrition, optimal rehabilitation and synergistic testosterone therapy in a clinically sound and resource-efficient fashion.
Humans ; Testosterone/therapeutic use* ; Retrospective Studies ; Male ; Hormone Replacement Therapy/methods* ; Intensive Care Units ; Singapore ; Middle Aged ; Muscle Weakness/drug therapy* ; Aged ; Hospitals, General ; Hand Strength ; Androgens/therapeutic use* ; Treatment Outcome ; Critical Illness/rehabilitation* ; Female ; Recovery of Function

Studies have investigated the effects of androgen deprivation therapy (ADT) use on the incidence and clinical outcomes of coronavirus disease 2019 (COVID-19); however, the results have been inconsistent. We searched the PubMed, Medline, Cochrane, Scopus, and Web of Science databases from inception to March 2022; 13 studies covering 84 003 prostate cancer (PCa) patients with or without ADT met the eligibility criteria and were included in the meta-analysis. We calculated the pooled risk ratios (RRs) with 95% confidence intervals (CIs) to explore the association between ADT use and the infection risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severity of COVID-19. After synthesizing the evidence, the pooled RR in the SARS-CoV-2 positive group was equal to 1.17, and the SARS-CoV-2 positive risk in PCa patients using ADT was not significantly different from that in those not using ADT (P = 0.544). Moreover, no significant results concerning the beneficial effect of ADT on the rate of intensive care unit admission (RR = 1.04, P = 0.872) or death risk (RR = 1.23, P = 0.53) were found. However, PCa patients with a history of ADT use had a markedly higher COVID-19 hospitalization rate (RR = 1.31, P = 0.015) than those with no history of ADT use. These findings indicate that ADT use by PCa patients is associated with a high risk of hospitalization during infection with SARS-CoV-2. A large number of high quality studies are needed to confirm these results.
Male ; Humans ; Prostatic Neoplasms/chemically induced* ; Androgen Antagonists/adverse effects* ; COVID-19 ; Androgens/therapeutic use* ; SARS-CoV-2

Most prostate cancers initially respond to androgen deprivation therapy (ADT). With the long-term application of ADT, localized prostate cancer will progress to castration-resistant prostate cancer (CRPC), metastatic CRPC (mCRPC), and neuroendocrine prostate cancer (NEPC), and the transcriptional network shifted. Forkhead box protein A1 (FOXA1) may play a key role in this process through multiple mechanisms. To better understand the role of FOXA1 in prostate cancer, we review the interplay among FOXA1-targeted genes, modulators of FOXA1, and FOXA1 with a particular emphasis on androgen receptor (AR) function. Furthermore, we discuss the distinct role of FOXA1 mutations in prostate cancer and clinical significance of FOXA1. We summarize possible regulation pathways of FOXA1 in different stages of prostate cancer. We focus on links between FOXA1 and AR, which may play different roles in various types of prostate cancer. Finally, we discuss FOXA1 mutation and its clinical significance in prostate cancer. FOXA1 regulates the development of prostate cancer through various pathways, and it could be a biomarker for mCRPC and NEPC. Future efforts need to focus on mechanisms underlying mutation of FOXA1 in advanced prostate cancer. We believe that FOXA1 would be a prognostic marker and therapeutic target in prostate cancer.
Humans ; Male ; Androgen Antagonists/therapeutic use* ; Androgens/metabolism* ; Hepatocyte Nuclear Factor 3-alpha/metabolism* ; Mutation ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Receptors, Androgen/metabolism*

We aimed to study radiomics approach based on biparametric magnetic resonance imaging (MRI) for determining significant residual cancer after androgen deprivation therapy (ADT). Ninety-two post-ADT prostate cancer patients underwent MRI before prostatectomy (62 with significant residual disease and 30 with complete response or minimum residual disease [CR/MRD]). Totally, 100 significant residual, 52 CR/MRD lesions, and 70 benign tissues were selected according to pathology. First, 381 radiomics features were extracted from T2-weighted imaging, diffusion-weighted imaging, and apparent diffusion coefficient (ADC) maps. Optimal features were selected using a support vector machine with a recursive feature elimination algorithm (SVM-RFE). Then, ADC values of significant residual, CR/MRD lesions, and benign tissues were compared by one-way analysis of variance. Logistic regression was used to construct models with SVM features to differentiate between each pair of tissues. Third, the efficiencies of ADC value and radiomics models for differentiating the three tissues were assessed by area under receiver operating characteristic curve (AUC). The ADC value (mean ± standard deviation [s.d.]) of significant residual lesions ([1.10 ± 0.02] × 10^-3 mm² s^-1) was significantly lower than that of CR/MRD ([1.17 ± 0.02] × 10^-3 mm² s^-1), which was significantly lower than that of benign tissues ([1.30 ± 0.02] × 10^-3 mm² s^-1; both P < 0.05). The SVM feature models were comparable to ADC value in distinguishing CR/MRD from benign tissue (AUC: 0.766 vs 0.792) and distinguishing residual from benign tissue (AUC: 0.825 vs 0.835) (both P > 0.05), but superior to ADC value in differentiating significant residual from CR/MRD (AUC: 0.748 vs 0.558; P = 0.041). Radiomics approach with biparametric MRI could promote the detection of significant residual prostate cancer after ADT.
Male ; Humans ; Prostatic Neoplasms/drug therapy* ; Androgen Antagonists/therapeutic use* ; Androgens ; Neoplasm, Residual ; Retrospective Studies ; Magnetic Resonance Imaging/methods* ; Diffusion Magnetic Resonance Imaging/methods*

Mitogen-activated protein kinase-8-interacting protein 2 (MAPK8IP2) is a scaffold protein that modulates MAPK signal cascades. Although MAPK pathways were heavily implicated in prostate cancer progression, the regulation of MAPK8IP2 expression in prostate cancer is not yet reported. We assessed MAPK8IP2 gene expression in prostate cancer related to disease progression and patient survival outcomes. MAPK8IP2 expression was analyzed using multiple genome-wide gene expression datasets derived from The Cancer Genome Atlas (TCGA) RNA-sequence project and complementary DNA (cDNA) microarrays. Multivariable Cox regressions and log-rank tests were used to analyze the overall survival outcome and progression-free interval. MAPK8IP2 protein expression was evaluated using the immunohistochemistry approach. The quantitative PCR and Western blot methods analyzed androgen-stimulated MAPK8IP2 expression in LNCaP cells. In primary prostate cancer tissues, MAPK8IP2 mRNA expression levels were significantly higher than those in the case-matched benign prostatic tissues. Increased MAPK8IP2 expression was strongly correlated with late tumor stages, lymph node invasion, residual tumors after surgery, higher Gleason scores, and preoperational serum prostate-specific antigen (PSA) levels. MAPK8IP2 upregulation was significantly associated with worse overall survival outcomes and progression-free intervals. In castration-resistant prostate cancers, MAPK8IP2 expression strongly correlated with androgen receptor (AR) signaling activity. In cell culture-based experiments, MAPK8IP2 expression was stimulated by androgens in AR-positive prostate cancer cells. However, MAPK8IP2 expression was blocked by AR antagonists only in androgen-sensitive LNCaP but not castration-resistant C4-2B and 22RV1 cells. These results indicate that MAPK8IP2 is a robust prognostic factor and therapeutic biomarker for prostate cancer. The potential role of MAPK8IP2 in the castration-resistant progression is under further investigation.
Male ; Humans ; Androgens/therapeutic use* ; Receptors, Androgen/genetics* ; Prognosis ; Mitogen-Activated Protein Kinase 8/therapeutic use* ; Cell Line, Tumor ; Prostatic Neoplasms/pathology* ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Gene Expression Regulation, Neoplastic

BACKGROUND: Till date, the optimal treatment strategy for delivering adjuvant androgen deprivation therapy (ADT) in localized and locally advanced prostate cancer (PCa), as a lower stage in PCa progression compared with metastatic PCa, is still unclear. This study compares the efficacy of castration alone with complete androgen blockade (CAB) as adjuvant ADT in patients with localized and locally advanced PCa undergoing radical prostatectomy (RP). METHODS: Patients diagnosed with PCa, without lymph node or distant metastasis, who received RP in West China Hospital between January 2009 and April 2019, were enrolled in this study. We performed survival, multivariable Cox proportional hazard regression, and subgroup analyses. RESULTS: A total of 262 patients were enrolled, including 107 patients who received castration alone and 155 patients who received CAB. The survival analysis revealed that there was no significant difference between the two groups (hazard ratios [HR] = 1.07, 95% confidence intervals [95% CI] = 0.60-1.90, P = 0.8195). Moreover, the multivariable Cox model provided similarly negative results before and after adjustment for potential covariant. Similarly, there was no significant difference in the clinical recurrence between the two groups in both non-adjusted and adjusted models. Furthermore, our subgroup analysis showed that CAB achieved better biochemical recurrence (BCR) outcomes than medical castration alone as adjuvant ADT for locally advanced PCa (P for interaction = 0.0247, HR = 0.37, 95% CI = 0.14-1.00, P = 0.0497). CONCLUSION Combined androgen blockade achieved better BCR outcomes compared with medical castration alone as adjuvant ADT for locally advanced PCa without lymph node metastasis.
Androgen Antagonists/therapeutic use* ; Androgens ; Castration ; Humans ; Male ; Neoplasm Recurrence, Local/pathology* ; Prostatectomy/methods* ; Prostatic Neoplasms/surgery* ; Retrospective Studies

OBJECTIVE: To evaluate the efficacy and safety of Pai-Neng-Da Capsule (, panaxadiol saponins component, PNDC) in combination with the cyclosporine and androgen for patients with chronic aplastic anemia (CAA). METHODS: A total of 79 CAA patients was randomly divided into 2 groups by a random number table, including PCA group [43 cases, orally PNDC 320 mg/d plus cyclosporine 5 mg/(kg·d) plus andriol 80 mg/d] and CA group [36 cases, orally cyclosporine 5 mg/(kg·d) plus andriol 160 mg/d]. All patients were treated and followed-up for 6 treatment courses over 24 weeks. The complete blood counts, score of Chinese medical (CM) symptoms were assessed and urine routine, electrocardiogram, hepatic and renal function were observed for safety evaluation. Female masculinization rating scale was established according to the actual clinical manifestations to evaluate the accurate degree of masculinization in female CAA patients treated by andriol. RESULTS: The effective rates were 88.1% (37/42) in the PCA group and 77.8% (28/36) in the CA group based on the standard for the therapeutic efficacy evaluation of hematopathy. There was no significant difference in the white blood cell (WBC) counts, platelet counts and hemoglobin concentration of peripheral blood between two groups after 6 months treatment. The masculinization score of female patient in the PCA group was significantly lower than the CA group (P<0.05). The mild abdominal distention was observed in 1 cases in the PCA group. In CA group, the abnormalities in the hepatic function developed in 2 cases and the renal disfunction was found in 1 case. CONCLUSION The PNDC possesses certain curative effects in the treatment of CAA without obvious side-effects and can partially replace andriol thereby to reduce the degree of masculinization [Registried at Chinese Clinical Trial Registry (ChicTR1900028153)].
Androgens ; Anemia, Aplastic/drug therapy* ; China ; Female ; Humans ; Nonprescription Drugs ; Saponins/therapeutic use*

The relationship between androgen and prostate cancer treatment has plagued the field of urologic oncology. To investigate the efficacy and safety of bipolar androgen therapy (BAT) followed by immune checkpoint inhibitor therapy in patients with metastatic castration resistant prostate cancer (mCRPC). In August 2020, Beijing Hospital conducted an investigator-initiated study: Bipolar androgen therapy followed by immune checkpoint inhibitor therapy in metastatic castration resistant prostate cancer. Up to now, the study has included 4 patients who completed the entire cycle of treatment. The mean age of the patients was 74.5 (68 to 82) years old, the mean prostate-specific antigen (PSA) was 20.8 (9.9 to 8.36) μg/L, the mean testosterone was 0.50 (0.00 to 1.81) μg/L, and the Gleason score were 10 and 9, 7, 7 respectively. The pain scale score before treatment was 1.5 (1 to 2). In this study, 4 patients completed the entire cycle of treatment, and the treatment effect of the patients showed great heterogeneity. PSA in case 1 decreased from 24.0 μg/L to 0.47 μg/L, testosterone increased from 0.175 6 μg/L to 2.62 μg/L. PSA in case 2 increased from 9.939 μg/L to 168.536 μg/L, and testosterone increased from 0.0 μg/L increased to 2.85 μg/L. PSA increased from 13.31 μg/L to 39.278 μg/L in case 3, testosterone increased from 0.0 μg/L to 2.54 μg/L. and PSA increased from 36.0 μg/L to 350.2 μg/L in the case 4, testosterone increased from 1.81 μg/L to 3.85 μg/L. Except for one patient who showed significant PSA remission, the PSA levels of the remaining three patients remained high overall. There were no adverse reactions reported in 4 patients. In the follow-up, case 1 continued to use PD-1 monoclonal antibody (median progression free survival time was 10 months). Two patients who had previously been resistant to enzalutamide received enzalutamide again after the whole cycle of treatment, and their PSA decreased again, which indicated that the patient was sensitive to enzalutamide again. BAT had a certain therapeutic effect on mCRPC patients, and the safety was controllable. Its tumor control effect still needed long-term follow-up verification in large-sample clinical trials. BAT has a certain therapeutic effect on mCRPC patient, especially the resensitivity of tumors to enzalutamide can be restored. Immune checkpoint inhibitors may have therapeutic potential in patients with prostate cancer treated with BAT and enzalutamide.
Aged ; Aged, 80 and over ; Androgens/therapeutic use* ; Humans ; Immune Checkpoint Inhibitors ; Male ; Nitriles/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Testosterone/therapeutic use* ; Treatment Outcome